Drosophila melanogaster males show a progressive loss of fertility with age. This reduction in fertility does not appear to be due to age-related changes in spermatogenesis but to a failure in other reproductive tract organs to produce sufficient seminal fluid. The proposed research will investigate the relationship between fertility loss in aging males and changes in the activity of an enzyme, esterase 6, which is highly concentrated in the anterior ejaculatory duct of males and is depleted during mating. Absolute amounts of esterase 6 present in aging males will be measured using immunological techniques. A second enzyme, NAD ion dependent sorbitol dehydrogenase, which serves as a marker for the development functional sperm will also be assayed. Age-dependent changes in the thermostability of esterase 6 will be followed to determine if posttranslational modification in this enzyme might affect fertility loss. It is hoped that these proposed investigations will show that fertility loss and related biochemical changes can serve as a model system in which the underlying biochemical mechanisms responsible for a clearly defined aging process can be elucidated.